Despite established, evidence-based therapies, major gaps exist in asthma treatment, increasing the risk of asthma-related emergency department visits, hospitalizations, and oral steroid bursts. Provider (therapeutic inertia, insufficient time, patient (poor adherence, smoking), and system barriers (challenges with data, monitoring, communication, and medication refill) contribute to these gaps. The application of Electronic Health Records (EHRs) has the potential to lower these barriers leading to better asthma control and fewer exacerbations. The objective of this study is to conduct a large pragmatic trial to assess the effectiveness, cost-effectiveness, and implementation of the Breathewell intervention, which combines an evidence-based EHR intervention and team-based care to improve asthma outcomes. Breathewell employs EpicCare, the most widely used commercial EHR in the U.S, to identify poor medication adherence or unaddressed smoking and automatically enroll patients in a medication refill or smoking cessation program. For patients with asthma exacerbations or B-agonist inhaler overuse, the EHR sends the patients a decision support tool and notifies a nurse who uses an EHR-generated report to engage the patient in a shared-decision discussion, leading to development of an asthma care plan. EHR templated notes and order sets facilitate care plan execution. The study will be conducted in 26 primary care clinics of Kaiser Permanente Colorado using a cluster- randomized pragmatic clinical trial design. More than 10,400 asthma patients will be assigned to Breathewell or Usual Care based on their clinic. The evaluation assesses clinical effectiveness (asthma exacerbations, quality of life, and cost) and implementation (mediators and moderators of intervention effect, intervention barriers and facilitators, patient and provider impressions and RE-AIM framework translational measures). This study is significant because it could substantially reduce morbidity by addressing gaps in evidence-based asthma care. This research is innovative because it 1) uses the EHR to simultaneously addresses provider, patient, and system barriers to evidence-based care; 2) facilitates patient-centered decision making; 3) integrates evidence-based EHR and interactive behavioral change technologies; 4) is conducted as part of routine clinical care; and 5) is delivered in English and Spanish. Our results are likely to impact the field by speeding the translation of asthma care knowledge into practice. Successful deployment of Breathewell could serve as an implementation model for using EHRs to improve care for many chronic conditions, an NIH research priority and an objective of Healthy People 2020.